• Philip Howles, PhD
  • Research Assistant Professor
  •  
  • Metabolic Diseases Institute
  • Phone: (513) 558-4288
  • philip.howles@uc.edu

Specialty/Interest:

  • Research in my lab is aimed at understanding the processes of lipid absorption and metabolism. These studies are especially relevant because of the rapid increase in obesity in developed countries and the consequent rise in Type II diabetes.

    In addition, hyperlipidemia is a major risk factor for cardiovascular diseases which remain a major couse of morbidity and mortality in "Western" cultures.

    One project is focused on elucidating the intracellular steps and cellular machinery that are involved in lipid absorption and chylomicron production by the intestinal epithelium.

    The second project is focused on the selective uptake of cholesterol esters from HDL by hepatocytes and the subsequent processing of that cholesterol for bile acid synthesis, lipoprotein production or secretion as biliary cholesterol.

    Both projects utilize knockout mice in which the gene for carboxyl ester lipase (CEL, cholesterol esterase, bile salt stimulated lipase) has been ablated.

    During active lipid absorption, these mice produce intestinal lipoproteins that are dramaticlly different in size and protein composition, suggesting that enzyme plays an important role in chylomicron synthesis and/or secretion - most likely by affecting Golgi function.

    Absence of a functional CEL gene also appears to alter the processing of HDL-cholesterol by hepatocytes, resulting in changes in bile acid production and biliary cholesterol secretion.

    All studies involve a combination of physiological, biochemical, and molecular techniques as well as both in vivo and in vitro (cell culture) systems. 

    Research Grants:

    • R01 HL078900 National Heart, Lung and Blood Institute. Carboxyl ester lipase affects hepatic HDL metabolism, PI, Active.
    • Department of Agriculture. Pancreatic Carboxyl Ester Lipase Influences Chylomicron Production and Metabolism, PI, Closed.
    • 5-R29-HD-33926-05-A0-S0-E0 National Institute of Child Health and Human Development. Lipid and Cholesterol Esterase in Neonatal Gut Integrity, PI, Closed.
    • SW-97-16-B-02-A0-S0-E0 American Heart Association - Southwest Chapter. Transcytosis and Vascular Tone in Caveolin-1 Deficient Mice, PI, Closed.
    • R01 DK076907 National Inst of Diabetes and Digestive and Kidney Disease. Physiological Role of NPC1L1 in Lipid Transport and Metabolism, Collaborator, Closed.
    • R01 DK076928 National Inst of Diabetes and Digestive and Kidney Disease. Functional and Molecular Study of Intestinal Cholesterol Transporters and Absorption, Collaborator, Active.
    • 07-MCG-20 National Inst of Diabetes and Digestive and Kidney Disease. Lymph Fistula Mouse: A Novel Model for Studying Incretin Secretion, PI, Closed.
    • 1 R01 DK077170-01A2 National Inst of Diabetes and Digestive and Kidney Disease. Role of NPC1L1 in Regulating Energy Metabolism, Nutrient Utilization and Weight Gain, PI, Active.
    • U24 DK059630 National Inst of Diabetes and Digestive and Kidney Disease. Cincinnati Mouse Metabolic Phenotyping Center, Collaborator, Active.

    Peer Reviewed Publications (in chronological order):

    • Basford, J. E., Wancata, L., Hofmann, S. M., Silva, R. A. G. D., Davidson, W. S., Howles, P. N., & Hui, D. Y. (2011). Hepatic Deficiency of Low Density Lipoprotein Receptor-related Protein-1 Reduces High Density Lipoprotein Secretion and Plasma Levels in Mice . The Journal of Biological Chemistry , 286 (15) , 13079-87.
    • Camarota, L. M., Woollett, L. A., & Howles, P. N. (2011). Reverse cholesterol transport is elevated in carboxyl ester lipase-knockout mice . The FASEB Journal : Official Publication of the Federation of American Societies For Experimental Biology , 25 (4) , 1370-7.
    • Yang, L., Li, X., Ji, Y., Kohan, A. B., Wang, D. Q., Howles, P. N., Hui, D. Y., Lai, J., & Tso, P. (2010). Effect of ezetimibe on incretin secretion in response to the intestinal absorption of a mixed meal . American Journal of Physiology. Gastrointestinal and Liver Physiology , 299 (5) , G1003-11.
    • Labonté, E. D., Camarota, L. M., Rojas, J. C., Jandacek, R. J., Gilham, D. E., Davies, J. P., Ioannou, Y. A., Tso, P., Hui, D. Y., & Howles, P. N. (2008). Reduced absorption of saturated fatty acids and resistance to diet-induced obesity and diabetes by ezetimibe-treated and Npc1l1-/- mice . American Journal of Physiology. Gastrointestinal and Liver Physiology , 295 (4) , G776-83.
    • Hui, D. Y., Labonté, E. D., & Howles, P. N. (2008). Development and physiological regulation of intestinal lipid absorption. III. Intestinal transporters and cholesterol absorption . American Journal of Physiology. Gastrointestinal and Liver Physiology , 294 (4) , G839-43.
    • Hui, D., E. Labonte and P. Howles (2008). Development and Physiological Regulation of Intestinal Lipid Absorption. III. Intestinal Transporters and Cholesterol Absorption . American Journal of Physiology & #8211; Gastrointestinal and Liver Physiology , 294 , G839-843.
    • Nogueiras, R., Wiedmer, P., Perez-Tilve, D., Veyrat-Durebex, C., Keogh, J. M., Sutton, G. M., Pfluger, P. T., Castaneda, T. R., Neschen, S., Hofmann, S. M., Howles, P. N., Morgan, D. A., Benoit, S. C., Szanto, I., Schrott, B., Schürmann, A., Joost, H., Hammond, C., Hui, D. Y., Woods, S. C., Rahmouni, K., Butler, A. A., Farooqi, I. S., & O (2007). The central melanocortin system directly controls peripheral lipid metabolism . The Journal of Clinical Investigation , 117 (11) , 3475-88.
    • Labonté, E. D., Howles, P. N., Granholm, N. A., Rojas, J. C., Davies, J. P., Ioannou, Y. A., & Hui, D. Y. (2007). Class B type I scavenger receptor is responsible for the high affinity cholesterol binding activity of intestinal brush border membrane vesicles . Biochimica Et Biophysica Acta , 1771 (9) , 1132-9.
    • Gilham, D., Labonté, E. D., Rojas, J. C., Jandacek, R. J., Howles, P. N., & Hui, D. Y. (2007). Carboxyl ester lipase deficiency exacerbates dietary lipid absorption abnormalities and resistance to diet-induced obesity in pancreatic triglyceride lipase knockout mice . The Journal of Biological Chemistry , 282 (34) , 24642-9.
    • Nogueiras, R., P. Wiedmer, D. Perez-Tilve, C. Veyrat-durebex, J. Keogh, G. Sutton, P. Pfluger, T. Castaneda, S. Neschen, S. Hofmann, P. Howles, D. Morgan, S. Benoit, I. Szanto, B. Schrott, A. Schurmann, H. Joost, C. Hammond, D. Hui, S. Woods, K. Rahmouni, A. Butler, I. Farooqi, S. O'Rahilly, F. Rohner-Jeanrenaud and M. Tschop (2007). The central melanocortin system directly controls peripheral lipid metabolism . Journal of Clinical Investigation , 117 , 3475-88.
    • Gilham,D., E. Labonte, J. Rojas, R. Jandacek, P. Howles and D. Hui (2007). Carboxyl ester lipase deficiency exacerbates dietary lipid absorption abnormalities and resistance to diet-induced obesity in pancreatic triglyceride lipase knockout mice . Journal of Biological Chemistry , 282 , 24642-24649.
    • Hui, D. Y., & Howles, P. N. (2005). Molecular mechanisms of cholesterol absorption and transport in the intestine . Seminars in Cell & Developmental Biology , 16 (2) , 183-92.
    • Camarota, L. M., Chapman, J. M., Hui, D. Y., & Howles, P. N. (2004). Carboxyl ester lipase cofractionates with scavenger receptor BI in hepatocyte lipid rafts and enhances selective uptake and hydrolysis of cholesteryl esters from HDL3 . The Journal of Biological Chemistry , 279 (26) , 27599-606.
    • Kirby, R. J., Howles, P. N., & Hui, D. Y. (2004). Rate of gastric emptying influences dietary cholesterol absorption efficiency in selected inbred strains of mice . Journal of Lipid Research , 45 (1) , 89-98.
    • Huggins, K. W., Camarota, L. M., Howles, P. N., & Hui, D. Y. (2003). (In Press). Pancreatic triglyceride lipase deficiency minimally affects dietary fat absorption but dramatically decreases dietary cholesterol absorption in mice. . The Journal of Biological Chemistry , 278 (44) , 42899-905.
    • Hui, D. Y., & Howles, P. N. (2002). (In Press). Carboxyl ester lipase: structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis. . Journal of Lipid Research , 43 (12) , 2017-30.
    • Kirby, R. J., Zheng, S., Tso, P., Howles, P. N., & Hui, D. Y. (2002). (In Press). Bile salt-stimulated carboxyl ester lipase influences lipoprotein assembly and secretion in intestine: a process mediated via ceramide hydrolysis. . The Journal of Biological Chemistry , 277 (6) , 4104-9.
    • Cai, S. F., Kirby, R. J., Howles, P. N., & Hui, D. Y. (2001). (In Press). Differentiation-dependent expression and localization of the class B type I scavenger receptor in intestine. . Journal of Lipid Research , 42 (6) , 902-9.
    • Shen, H., Howles, P., & Tso, P. (2001). (In Press). From interaction of lipidic vehicles with intestinal epithelial cell membranes to the formation and secretion of chylomicrons. . Advanced Drug Delivery Reviews , 50 Suppl 1 , S103-25.
    • Howles, P. N., Stemmerman, G. N., Fenoglio-Preiser, C. M., & Hui, D. Y. (1999). (In Press). Carboxyl ester lipase activity in milk prevents fat-derived intestinal injury in neonatal mice. . The American Journal of Physiology , 277 (3 Pt 1) , G653-61.
    • Carter, C. P., Howles, P. N., & Hui, D. Y. (1997). (In Press). Genetic variation in cholesterol absorption efficiency among inbred strains of mice. . The Journal of Nutrition , 127 (7) , 1344-8.
    • Howles, P. N., Carter, C. P., & Hui, D. Y. (1996). (In Press). Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice. . The Journal of Biological Chemistry , 271 (12) , 7196-202.